Tuesday, November 13, 2007
A drug currently used to treat high blood pressure and heart failure has been found to reduce the symptoms of multiple sclerosis in mice. The discovery that amiloride can reduce the degeneration of nerve tissue in mice suggests it could have a therapeutic potential for people who have MS. However, despite the positive findings, the researchers warn that clinical trials in people, to test the drug's full potential, are crucial before it is given as a treatment for the disease.
The research led by Professor Lars Fugger of the Medical Research Council Human Immunology Unit and Department of Clinical Neurology at Oxford University is published in Nature Medicine. Professor Fugger said:
''This drug [amiloride] is already licensed for another purpose. Looking for new ways to use established drugs is usually cheaper than starting the discovery process from scratch, we've had a really positive result.''
The search for therapeutic potential began with studies of the role of a channel called ASIC1 that creates an opening in the cell membrane. ASIC1 works by sensing acid levels around the cell and lets sodium and calcium molecules into cells. This process is an important part of the process of sensing pain and touch. Using mice with a condition that mimics some aspects of the human form of multiple sclerosis the scientists found that the ASIC1 channel also contributes to degeneration of the axon, the long stem of the nerve. When the channel remains open, sodium and calcium can flood into the cell in higher than normal proportions.
Professor Fugger explained:
''When sodium and calcium levels accumulate in excessive proportions within nerve cells, the axon, the bit that carries messages from one nerve to the next, is damaged. We found that this damage was reduced in mice given amiloride. The drug appears to work by blocking the action of the channel that lets sodium and calcium molecules into the cell.''
The research has shown that not only is the ASIC1 channel a suitable target for drugs that aim to protect against neurodegeneration in research but that amiloride might be beneficial in treatment.
Overall this suggests that drugs targeted at the ASIC1 channel, like amiloride, could help reduce the level of nerve damage caused by multiple sclerosis. The research team are now beginning to plan a clinical trial that will aim to find out if amiloride is beneficial in treating the symptoms of multiple sclerosis in people.
Original research paper: Acid-sensing ion channel 1 contributes to axonal degeneration in autoimmune inflammation of the central nervous system is published in Nature Medicine.